1. Brief Description of Patient Groups Supplying Input

Two patient groups provided patient input for this submission: the Gastrointestinal (GI) Society and Crohn’s and Colitis Canada (CCC).

The GI Society is committed to improving the lives of people with GI and liver conditions by supporting research, advocating for patient access in health care, and promoting GI and liver health. It provides evidence-based information through the BadGut basics patient information pamphlet and the Inside Tract/Du Coeur au ventre newsletter, BadGut lectures, GI support group meetings, continuing education events for health care professionals, and a website in English (www.badgut.org) and French (www.mauxdeventre.org). In the last two years, the GI Society has received funding from AbbVie Corporation, Actavis/Allergan, AstraZeneca Canada Inc., Ferring Inc., Gilead Sciences Canada Inc., GlaxoSmithKline Inc., Hoffmann-La Roche Limited, Innovative Medicines Canada, Janssen Canada, Johnson & Johnson, LifeScan, Merck Canada Inc., Pfizer Canada Inc./Hospira, Shire Canada Inc., and Takeda Canada Inc.

Crohn’s and Colitis Canada (CCC) is a volunteer-based national charity dedicated to investing in education, awareness, and research for Crohn’s disease (CD) and ulcerative colitis. CCC has received funding from individual donors and various pharmaceutical companies. In the 2014–2015 fiscal year, CCC received less than 11% of its total revenue from pharmaceutical companies, of which none were formally mentioned in their submission.

Both the GI Society and CCC have declared no conflict of interest with regard to the preparation of their submissions.

2. Condition-Related Information

The information in this section was collected through patient and caregiver interviews; a 2011 national survey conducted by the CCC; focus groups; a Canadian questionnaire conducted by the GI Society; patient roundtables; various interactions by telephone, email, and social media; stories obtained via patients over time; and a review of CCC published reports.

Crohn’s disease is a disabling, lifelong inflammatory bowel disease (IBD), which is characterized by inflammation that can extend through the entire thickness of the bowel wall. According to the patient groups, Canada has the highest prevalence of CD in the world, with approximately 129,000 diagnosed patients. The disease can have a profound effect on patients’ physical, emotional, and social well-being. In the patient input submissions, the groups expressed that the uncertainty of where and when the next flare will occur may lead to anxiety and stress, and may limit the places patients can go and/or the activities they participate in (including work and school). As one patient stated, “It makes it difficult to leave my house, play with my son, work, etc. when I am in a flare.” This finding is supported by the CCC 2011 survey, which found that 43% of employed patients with IBD took some time off work, with an average of 7.2 missed days per year. Furthermore, 34% of respondents frequently were unable to play sports, 22% missed school trips, 40% avoided parties, and 22% did not attend special events.

Although the most commonly reported symptoms of IBD include bloody diarrhea, bloating, abdominal pain, and fatigue, the patient groups also noted that CD can lead to anemia, weight loss, fever, arthritis, ulcers of the mouth or skin, tender and inflamed nodules on the shins, and delayed development in children. The groups also reported that some patients were concerned about the increased risk of colon cancer with longstanding CD. The submissions noted two key concerns among patients with IBD. The first is the lack of control over bowel movements, including the urgent and frequent need to go to a bathroom. The CCC 2011 survey found that 73% of IBD patients reported five to 20, or even more, bowel movements per day. As one patient said, “When you have to go to the washroom 20 times a day, it impacts everything you do.” The second major patient concern was a fear of flares and the desire for sustained remission, which has been suggested to be more important than relieving any one symptom of IBD. Concerns about future flares and uncertainty about their severity and occurrence were captured in numerous patient comments:

“When I’m not in an active flare I live in constant fear of when the next flare will occur.”

“The worst part is fearing the next big flare that will prevent me from being a mom to my 18-month-old.”

Patient groups also reported an impact on caregivers, highlighting the inability of those who care for patients with CD to work and complete day-to day tasks, as well as the fatigue and stress associated with caregiving. Many caregivers lose their personal time to take on additional responsibilities that the person suffering from CD may no longer be able to complete. In addition, they may feel isolated and disempowered.

3. Current Therapy-Related Information

Management of CD is described as multi-faceted: it involves both symptom control and targeting of the underlying inflammation. Both submissions noted a lack of treatments available for CD. First-line therapy is aminosalicylates (e.g., 5-ASA, mesalamine) with steroids. If remission is not achieved or if the condition worsens, second-line therapy is immunomodulators (e.g., azathioprine), sometimes combined with corticosteroids (e.g., prednisone) and biologics. Patients reported few side effects with aminosalicylates, whereas some patients reported liver problems with immunomodulators. By contrast, the majority of patients reported side effects from steroids, the most common being mood swings, “moon face,” and weight gain. Suppository formulations of corticosteroids are available, but patients find these inconvenient and say suppositories do not allow patients to maintain a normal routine. In addition, while these drugs may be effective in patients with mild-to-moderate disease, they often fail to maintain remission in the long-term, and are ineffective for moderate-to-severe disease. Interviews with patients suggested that these treatments help relieve some symptoms but do not offer control, as the need for constant and urgent washroom use remained. For patients who do progress to biologics, the cost and accessibility issues associated with them are important.

When the first- and second-line therapies fail to provide symptom relief, biologics are often considered effective to avoid surgery for patients with CD. The large majority of surveyed patients said they would rather receive a biologic, despite its potential risks and side effects, than undergo a colectomy. As noted by one patient, “I have a strong desire to keep my body intact. The colon serves a myriad of beneficial functions.” According to the GI Society, surgical removal of the colon is not recommended by physicians in patients suffering from CD, as the disease can affect the entire GI tract and extend into the muscle wall. Patients further noted that surgery can be associated with later complications, including soiling, even more liquid bowel movements, poor pouch function, pouchitis, sexual dysfunction, and an increased risk of fertility loss among women. Surgery should only be considered as a last resort. Patients expressed their concern about surgery and the lack of treatment options available to them: “Proposing surgery as a viable treatment option is inhumane and not fair. Surgery should be considered an option of last resort. It is a shame that there is nothing else to take.”

4. Expectations About the Drug Being Reviewed

Patients hope that ustekinumab will provide them with another biologic option in their arsenal against CD, especially when other biologics either do not work or cease to work. Further, they hope that ustekinumab will provide them with a better quality of life — a life that is more normal and stable with less suffering from the effects of CD. In addition, they hope that ustekinumab will help to confer long-term remission from CD. Patients also find the route of administration (injection) appealing, as it will reduce the need to travel to infusion centres. However, the cost of ustekinumab is also a concern of patients, and many are worried that it will not be reimbursed.

One patient who responded and was currently receiving ustekinumab indicated that this was her third biologic in the last 16 years. She had first received infliximab (Remicade) for eight years before losing response and then trying adalimumab (Humira), which failed to treat CD. During the course of adalimumab, she had two additional bowel operations. Another patient who had experience with ustekinumab was able to avoid having irreversible surgery (removal of rectum) and was grateful to have received the drug. In addition, one other patient (who had both plaque psoriasis and CD) who received ustekinumab said that the drug eliminated the need for invasive and concurrent medication and greatly improved her quality of life.

Each case of CD is unique; physicians treating individual patients must take into account individual comorbidities and influences. What works for one person does not necessarily work for another. Choice among effective treatment options is essential for patients.